Two different corticotropin-releasing factor (CRF) receptors, CRF1 and CRF2, have been identified in rat and human brain. Although the two receptor subtypes show a markedly different distribution in the rat brain, their distribution in the primate brain has not been described previously. In this study, the neuroanatomic distribution of CRF1 and CRF2 receptor binding sites in rhesus monkey (Macaca mulatta) was assessed by using iodine 125 ([125I)-Tyr0]-sauvagine with or without the selective CRF1 receptor antagonist CP-154,526-1. Radiolabeled human cRNA probes were used to map the distribution of the two receptor mRNAs with in situ hybridization. Both CRF1 and CRF2 receptors were found in the pituitary and throughout the neocortex (especially, in prefrontal, cingulate, striate, and insular cortices), amygdala, and hippocampal formation of the monkey brain. This is in contrast to the distribution of these receptors reported in the rat brain, in which generally only the CRF1 receptor is found in the pituitary and neocortex. These results suggest that, in primates, both CRF1 and CRF2 receptors may be involved in mediating the effects of CRF on cognition, behavior, and pituitary-adrenal function. The presence of CRF1 (but not CRF2) receptors within the locus coeruleus, cerebellar cortex, nucleus of the solitary tract, thalamus, and striatum and of CRF2 (but not CRF1) receptors in the choroid plexus, certain hypothalamic nuclei, the nucleus prepositus, and the nucleus of the stria terminalis suggests that each receptor subtype also may have distinct functional roles within the primate central nervous system.